Myelin basic protein (MBP) is one of the major protein components of the CNS myelin sheath. The protein is closely associated with the inner folds of the myelin membrane where it provides stability to the multilamellar structure. Autoimmune responses to MBP have been implicated in the demyelinating diseases experimental allergic encephalomyelitis and multiple sclerosis. The exact mechanism of the interaction between MBP and the myelin membrane is not well understood. It has been suggested, however, that the methylation of the protein on Arginine-107 is an important aspect of the microscopic interaction mechanism. This residue is methylated by reaction with S-adenosylmethionine (SAM), although the enzyme catalyzing this methylation has not been purified. In order to more completely understand the mechanism of the myelin-MBP interaction, we propose to isolate and purify the enzyme system responsible for the methylation reaction. This enzyme will be characterized kinetically and the mechanism of the methylation reaction will be investigated. The role of the methylated arginine in the myelin-MBP interaction will be investigated with special emphasis on the suggestion that a deficiency in methylation may be associated with increased susceptibility to demyelinating diseases. The mechanism of lamellae destabilization during the phagocytosis of myelin will be investigated with special emphasis on the role of lysosomal pH gradients in primary and "bystander" demyelination. This work will directly contribute to our understanding of the chemical and kinetic mechansisms of methyltransferase enzymes, the physiological consequences of the methylation of MBP and will approach an understanding of the mechanisms of cell-mediated myelin degeneration in multiple sclerosis and similar demyelinating diseases.